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Biomedical subjects

Alberto Pignone

Publications and source records attributed to Alberto Pignone.

12 recordsLinked to original sources
PubMed2006

Proton magnetic resonance spectroscopy reveals central neuroaxonal impairment in systemic sclerosis.

OBJECTIVE: . Involvement of the central nervous system (CNS) in systemic sclerosis (SSc) is rare. Proton magnetic resonance spectroscopy (1H-MRS) assesses in vivo cerebral metabolites. We investigated the biochemical modifications of the CNS in SSc. METHODS: N-acetylaspartate/creatine ratio (NAA/Cr) and choline/creatine ratio (Cho/Cr) at right centrum semiovale (RCS) and at right basal ganglia (RBG) were evaluated by 1H-MRS in 12 patients with limited (lSSc) and 8 patients with diffuse SSc (dSSc) and 20 control subjects. RESULTS: With 1H-MRS, a significant reduction of NAA/Cr ratio at RBG (p < 0.02) and at RCS (p < 0.002) was detected in SSc patients. Cho/Cr ratio was increased (p < 0.02) in the RCS, but not in RBG. In patients with lSSc, a significant reduction of NAA/Cr was detected in RCS but not in RBG. CONCLUSION: Evidence of neuroaxonal damage strongly suggests the existence of CNS involvement in SSc.

Adult↗
PubMed2006

Resistance to apoptosis in circulating alpha/beta and gamma/delta T lymphocytes from patients with systemic sclerosis.

OBJECTIVE: T cell activation plays a pivotal role in the immunopathogenesis of systemic sclerosis (SSc). Lymphocyte processes are tightly controlled by molecules activating either proliferation or programmed cell death (apoptosis). We investigated whether an imbalance in apoptotic function, increasing the survival rate of autoreactive cells, may lead to persistent autoreactive phenomena. METHODS: We studied peripheral a/b and g/d T lymphocytes of 22 patients with SSc and 22 healthy controls for their spontaneous and stimulated (phytohemagglutinin, dexamethasone) apoptotic rate and surface phenotype including expression of Fas (CD95) and Bcl-2, determined by flow cytometry. sFas and sFas ligand in sera and supernatants were measured by ELISA. Caspase-3 activation in response to agonistic anti-Fas Mab treatment was assessed. RESULTS: Lymphocytes of SSc patients showed a significant decrease in the percentage of apoptotic cells over time, in both unstimulated and stimulated cultures, compared to controls. We observed no difference between patients and controls, in stimulated or unstimulated cells, in the phenotypic expression of apoptotic cells, including surface Fas. SSc T cells were less susceptible to undergoing apoptosis after anti-Fas stimulation. We observed a significant decrease of apoptotic cells from stimulated culture of isolated SSc g/d T cells. Serum levels of sFas in SSc patients were significantly higher compared to controls. Similar data were obtained in the supernatants of stimulated and unstimulated cultures. By contrast, sFas ligand was always reduced. Bcl-2 expression in SSc was significantly elevated. A significant decrease in caspase-3 activity was detected in SSc patients after treatment by agonistic anti-Fas antibody. CONCLUSION: Resistance to apoptosis is present in a/b and g/d T cell lymphocyte subsets of patients with SSc, and several pathways seem to be connected in this setting.

Adult↗
PubMed2004

Health-related quality of life in systemic sclerosis as measured by the Short Form 36: relationship with clinical and biologic markers.

OBJECTIVE: To evaluate health-related quality of life (HRQOL) in patients with systemic sclerosis (SSc) using the Short Form 36 (SF-36) and to correlate SF-36 scores with clinical and biologic markers. METHODS: The SF-36 was administered to 24 controls and 24 SSc patients. SSc patients also were evaluated for subset (limited SSc [lSSc] and diffuse SSc [dSSc]), age, disease duration, angiotensin-converting enzyme (ACE) levels, autoantibodies, and skin and internal organ involvement. RESULTS: The physical summary score (PSS) was lower in SSc patients than in controls (P < 0.05), whereas the mental summary score (MSS) was higher in dSSc than in lSSc patients (P < 0.05). Five of 8 single SF-36 domain scores were lower in SSc patients than in controls (P < 0.05). Vitality was higher in dSSc than in controls (P < 0.001). In SSc, elder age correlated with lower PSS; low ACE levels and high skin score correlated with higher general mental health and role limitations due to physical problems, respectively (P < 0.05). Patients with heart involvement had higher scores in general health perceptions (P < 0.05). CONCLUSION: The SF-36 shows that HRQOL is impaired in patients with SSc. Higher scores in MSS and vitality in patients with dSSc and correlations of high SF-36 scores with specific organ involvement suggest that SSc patients with severe disease are more able to cope with HRQOL modification.

Adaptation, Psychological↗
PubMed2004

Dimensions of psychological dysfunction in patients with fibromyalgia: development of an Italian questionnaire.

Our objective was to observe whether dysfunctional psychological dimensions of pain could be detected in fibromyalgia patients through the development of a new questionnaire. An original questionnaire composed of 51 items was given to 250 patients (185 females and 65 males, mean age 55+/-12.8 years) suffering from chronic fibromyalgia according to the criteria of the Multicenter Criteria Committee of the American College of Rheumatology. A Varimax computerized program of factorial analysis with orthogonal and oblique rotation of the axes was used to analyze the data. Five strong independent factors were identified: 1) catastrophizing and 2) external control beliefs (cognitive); 3) alexithymia (emotional); 4) restless behavior (behavioral); and 5) need for support (relational). Our questionnaire is a preliminary development of an Italian language psychological characterization of FM patients which may be a relevant and useful tool for the evaluation of the outcome of clinical/psychological treatment of FM.

Chronic Disease↗
PubMed2003

Current Treatment Options in Raynaud's Phenomenon.

The treatment of Raynaud's phenomenon (RP) strictly depends on the severity of symptoms and on the presence of an underlying systemic disease. For this reason, any patient with RP should be carefully assessed for signs and symptoms that may herald an underlying disease. Primary RP can usually be managed with conservative nonpharmacologic lifestyle modifications (eg, avoidance of cold temperatures, tobacco, caffeine, and any drug interfering with vascular tone) and pharmacologic treatment added only if attacks are poorly controlled. Vasodilating drugs (eg, calcium channel blockers, angiotensin II receptor antagonists, topical nitrates, and prostanoids) are still the mainstay of medical therapy for RP. Anecdotal reports with different kinds of therapies appear regularly but always need evidence-based confirmation. In particular, antioxidant agents may be useful in limiting the progressive endothelial damage. Novel therapeutic tools interfering either with primary or secondary pathogenetic processes (ie, endothelial and peripheral nervous system dysfunction and smooth muscle cell hypertrophy) are awaited.

Journal Article↗
PubMed2003

Pupillocynetic activity of substance P in systemic sclerosis.

OBJECTIVE: In systemic sclerosis (SSc), dysfunctions of peripheral nervous system (PNS) have been observed. Substance P (SP) instillation in human eye induces a cholinergic-independent pupil myosis. Pupil basal diameters (PBD) and pupil responsiveness to SP, expressed as area under the curve (AUC), were studied by pupillometry to assess SP-ergic fiber state and function in SSc. METHODS: Forty SSc patients [24 with limited (lSSc), 16 with diffuse (dSSc) disease] and 40 controls underwent pupillometric evaluation. After evaluation of PBD, SP 10-3 M was instilled in one eye and placebo in the contralateral eye. Antinuclear (ANA), anticentromere (ACA), and anti-Scl-70 autoantibodies were correlated with PBD and AUC. RESULTS: PBD was significantly lower in SSc patients versus controls (p < 0.001). PBD was minor in lSSc versus both dSSc and controls (p < 0.05), but no difference was found between dSSc and controls. In SSc, SP 10-3 M induced greater myosis compared to controls (p < 0.001). SP 10-3 M-induced myosis was higher in lSSc versus both dSSc and controls (p < 0.05). ACA significantly correlated with decreased values of PBD and AUC (p < 0.001). CONCLUSION: Our results show that PBD is reduced in patients with SSc and that SP induces a more intense myosis in SSc than controls. Moreover, in lSSc PBD is lower and SP increases the myosis in lSSc compared to dSSc and controls. This suggests a peculiar dysfunction of PNS in patients with the limited subset of SSc.

Aged↗
PubMed2002

High prevalence of polymorphisms of angiotensin-converting enzyme (I/D) and endothelial nitric oxide synthase (Glu298Asp) in patients with systemic sclerosis.

PURPOSE: Systemic sclerosis is characterized by progressive microvascular occlusion and fibrosis and by an imbalance in the fibrinolytic system. In vivo and in vitro studies suggest that the renin-angiotensin system partly regulates vascular fibrinolytic balance. Angiotensin II increases the production and secretion of plasminogen activator inhibitor-1, while angiotensin-converting enzyme (ACE) contributes to reduced production of tissue plasminogen activator and endothelial nitric oxide synthesis by bradykinin degradation. The aim of our study was to investigate the effects of ACE insertion/deletion (I/D) and endothelial nitric oxide synthase (eNOS) Glu298Asp (G894-->T) and T-786-->C polymorphisms in patients with systemic sclerosis. SUBJECTS AND METHODS: We studied 73 consecutive patients (47 with limited and 26 with diffuse cutaneous systemic sclerosis) and 112 control subjects. ACE I/D and eNOS polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The ACE I/D and the eNOS G894-->T polymorphisms were more common in patients than in controls (for the ACE D allele: odds ratio [OR] = 3.4; 95% confidence interval [CI]: 1.5 to 7.9; P = 0.003; for the eNOS T allele: OR = 1.9; 95% CI: 1.0 to 3.4; P = 0.04). There was no association between the eNOS T-786-->C polymorphism and systemic sclerosis. CONCLUSIONS: Our findings of an increased risk of systemic sclerosis in ACE D and eNOS 894T allele carriers suggest that these polymorphisms may contribute to the pathogenesis of the disease.

Adult↗
PubMed2002

Effect of N-acetyl-L-cysteine on peroxynitrite and superoxide anion production of lung alveolar macrophages in systemic sclerosis.

Lung macrophages may play a relevant role in oxidative processes producing both superoxide anion (O(2)(-)) and NO. In this view, an antioxidant therapy can be useful in the treatment of systemic sclerosis (SSc) patients. N-Acetylcysteine (NAC) is able to expand natural antioxidant defenses by increasing intracellular gluthatione concentration and it has been proposed as an antioxidant therapy in respiratory distress syndromes. The aim of our study was to determine whether lung macrophages obtained from SSc patient bronchoalveolar lavage (BAL) express the inducible form of nitric oxide synthase (iNOS) and whether NAC can reduce the peroxynitrite (ONOO(-)) and O(2)(-) production of these cells. Alveolar macrophages were isolated from BAL of 32 patients and used for the immunocytochemical determination of iNOS, and the production of ONOO(-) and O(2)(-) was measured by fluorimetric or spectrophotometric methods, respectively. Lung macrophages obtained from SSc patients expressed a higher level of iNOS compared to healthy subject cells. NAC preincubation (5 x 10(-5)M, 24h) significantly reduced (-21%) the ONOO(-) production in formyl Met-Leu-Phe (fMLP)-activated cells and slightly reduced it under resting conditions, whereas NAC preincubation was unable to modify the release of O(2)(-) both in basal condition and in fMLP-stimulated cells. We conclude that since SSc lung macrophages express high levels of iNOS and produce a significant quantity of ONOO(-), NAC administration reduces ONOO(-) production and can be an useful treatment to alleviate SSc symptoms.

Acetylcysteine↗
PubMed2002

The pathogenesis of inflammatory muscle diseases: on the cutting edge among the environment, the genetic background, the immune response and the dysregulation of apoptosis.

Inflammatory muscle diseases (IMD), including dermatomyositis (DM) and polymyositis (PM), affect skeletal muscle, leading to profound tissue modification. The etiology of IMD is unknown, but multiple steps of the disease pathogenesis have been identified. The main alterations involve the immune response. Cellular infiltrates found in the muscle provide strong evidence for the involvement of a preferential immune mechanism of muscle damage. The pathologic differences found between PM and DM indicate a different role played by cell-mediated and humoral immune alterations. It is well accepted that in the pathogenetic pathway both host genes and environmental factors are involved. Apoptosis, or programmed cell death, is a complex process that plays a key role in many physiological events. It regulates the turnover of immune cells and is one of the mechanisms involved in ensuring a competent, non-autoreactive repertoire of lymphocytes. Apoptosis as a mechanism of muscle fibre death has been described in several neuromuscular disorders and muscular dystrophies, and evidence of a lack of apoptosis in IMD suggests a failure of apoptotic clearance of inflammatory cells playing a role in the maintenance of chronic cytotoxic muscle fibre damage. Most likely, the failure of apoptosis seems to be the main hallmark of the pathogenesis of IMD.

Apoptosis↗
PubMed2002

Overlap syndromes.

Many connective tissue diseases share common signs and symptoms, which frequently makes the diagnosis of a specific rheumatic disease difficult. Rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, polymyositis, dermatomyositis (DM), mixed connective tissue disease, and Sjögren's syndrome can present with similar clinical features, particularly during the first 12 months of symptoms. Overall, a rheumatic disease can appears in conjunction with features of one or more other connective tissue diseases, for example, patients can have a combination of rheumatoid arthritis and systemic lupus erythematosus ("rhupus"), or systemic sclerosis and polymyositis, defining an "overlap syndrome", where the diseases comply with the diagnosis criterias. Finally, when a person has symptoms of various connective tissue diseases without meeting the full criteria for any one of them, it is often called Undifferentiated Connective Tissue Disease.

Connective Tissue Diseases↗